While progress has been made in the fields of modern bio-science and medicine in the past few decades, basic methodologies, approaches and, to the largest extent, instruments in the above mentioned areas have remained fundamentally the same. This has resulted in a relative lack of major breakthroughs in key areas such as early deadly disease detection (i.e., cancer), effective and targeted drug release and effective disease treatments. As an example, treatment options for cancer, heart disease and diabetes still remain limited.
For example, various imaging techniques such as nuclear magnetic resonance (“NMR”) and computerized tomography scans (“CT Scans”) have been developed to better diagnose diseases via their improved resolutions. In the field of cancer detection, recently emerging detection processes involve the use of an immunological approach with tissue-specific gene expression identification targeting processes which utilize the aid of technologies such as micro-electro-mechanical systems (“MEMS”). See K. Patel, et al., Nature Reviews, Vol. 8, pp 329 (2008). However, most of these techniques remain too macroscopic and lack a high degree of sensitivity and effectiveness for early stage detection of many deadly diseases such as cancer. At best, the usefulness of these techniques is limited to certain forms of diseases and to very limited locations within the human body, at the mid to late stages of disease. While newer detection technologies utilizing an immunological approach and a tissue-specific gene expression identification targeting process mentioned above are being experimented for improved testing sample size, speed, and sensitivity, none of them has been clinically successful at identifying diseases such as cancer at an early stage with required sensitivity and specificity. Most of them require the use of complicated sample enrichment, marker chemistry, system calibration and/or data interpretation.
In the area of disease treatment for deadly diseases such as cancer, many current treatment techniques often lack effectiveness, selectivity and specificity. At the same time, many treatment approaches result in side effects. Specifically, for cancer treatment, most of the common approaches including radiation, chemotherapy, surgery and a combination of the above technologies have not been effective for many types of cancer at the mid to late stages of the cancer, have significant side effects and lack specificity to targeted cancerous areas and cells. In addition, cancer treatment is often very expensive. In cases where treatment is effective initially, cancer cells often develop resistance (especially with a number of platinum-based cancer drugs) and/or spread (metastasize) to other locations such as liver and lung. Recent experiments with angiogenesis inhibitor therapy, hyperthermia therapy, biological therapy and targeted treatments (see B. Zahorowska et al., J. Cancer Res Clin Oncol, published online (June 17, 2009), for a review on targeted therapies) utilizing nano-particles for drug delivery and molecular modulated targeting using desired drugs or substance have shown some degree of promise. However, to date, none of these mentioned approaches have been fully proven in large sample clinical trials. Often, they introduce additional types of side effects such as the resulting of a compromised immune system.
One of the major challenges in the treatment of deadly diseases such as cancer is that drugs often cannot be effectively delivered to its intended target and/or sufficiently absorbed by the targeted cancer cells. Even if the drug has reached its intended target site and proven to be effective to diseased organs, tissues and cells, most of the drugs lack treatment selectivity, resulting in damage to normal organs, tissues, and cells as well as the resulting undesirable side effects. In recent years, nano-technologies utilizing nano-sized particles ranging in size from 100 nanometers to a few microns have been proposed and evaluated for improved drug delivery performance. (See S. D. Smedt, J. Am. Chem. Soc. 130, pp. 14480-14482 (2008); A. L. Z. Lee, et al., Biomaterials, 30, pp. 919-927 (2009); T. Desai, Nano Lett. 9, pp. 716-720 (2009); R. O. Esenaliev, U.S. Pat. No. 6,165,440; P. S. Kumar, et al., U.S. Pat. No. 7,182,894; C. J. O'Conner, et al., US Patent Application number 20020068187; S. A. Herweck, et al., US Patent Application number 20040236278; H. Hirata, et al., US Patent Application number 20070243401; G. S. Yi, et al., US Patent Application number 2009008146).
Most of the proposed approaches using nano-particles cited above lack the following basic functions and abilities: (a) to reach its targeted location in a controlled manner, (b) selectivity and specificity to its intended targets (such as cancer cells), (c) the ability to avoid interactions with the environment on its way to its intended target(s), (d) a controlled release mechanism at a microscopic level (for example, releasing drug only to a specific cell and not to its surrounding area), and (e) bio-degradability of the nano-particle after its use. Very few have contemplated approaches which selectively target treatment sites. A. Chauhan, et al., disclosed a drug delivery system comprising a contact lens in which nano-particles are dispersed with drug encapsulated within said nano-particles (See US Patent Application number 20040096477). J. S. Minor, et. al. (US patent application number 20060040390) proposed the use of a biological “key” molecule to recognize targets. A. Manganaro, et al. proposed a method (US patent application number 20080279764) in which an ascorbate on the surface of nano-carrier is used to react with the super oxides produced by the cells, with an expected result of enhanced reactions between anti-cancer agent in the carrier and the cancer cells. While the above mentioned prior art attempts to target treatment, the applicability is relatively narrow and lacks the ability to target a wide range of cells, tissues, organs and diseases. Further, the “key” molecule or ascorbate on the surface of nano-carriers mentioned in the Minor application and the Manganaro application are likely to react with the environment in the living body and will thus have many difficulties in reaching its intended targets while still in its original form.
While the above-cited approaches have shown some potential merits over conventional approaches, they have not fundamentally solved the controllability, selectivity and specificity problems in drug delivery. For example, nano-particles coated with a designed drug onto their surface do not necessarily prevent the drug from interacting with various bio-chemical systems along their way to the targeted delivery location; nor do they have the intrinsic capabilities of selective delivery to diseased organs, tissues or areas within the body.
In recent years, certain types of micro-chips such as MEMS have been utilized for a number of bio-medical related applications. However, most of these applications involve relatively simple micro-chips with limited functions and for relatively narrowly focused applications in the field of bio-medicine. Mainly, these applications are limited to imaging (for example, Durack, U.S. Pat. No. 7,590,221), sensing (for example, Liu, et al., U.S. Pat. No. 7,661,319) and genomics related analysis and mapping (for example, Harris, et al., U.S. Pat. No. 7,635,562). Novel device fabrication processes disclosed in this patent application for bio-medical applications using microelectronics processes are clearly differentiated from the prior art cited above in unique process flows, utilization of the most advanced microelectronics processing technologies, degree of integration, and ability to fabricate devices with a much higher degree of functionality and flexibility.
To overcome the above-mentioned, long unresolved problems, a new and novel method utilizing current nano-technological processes for fabricating a range of micro-devices with significantly expanded capabilities, unique functionalities at microscopic levels, an enhanced degree of flexibilities, reduced costs and improved performance in the fields of bioscience and medicine is disclosed in the within patent application. Micro-devices fabricated using the disclosed nano-technological techniques have significant improvements in many areas over the existing, conventional methods. Such improvements include, but are not limited to, reduced overall costs, early disease detection, targeted drug delivery, targeted disease treatment and reduced degree of invasiveness in treatment. Compared with existing, conventional approaches, the said inventive approach disclosed in this patent application is much more microscopic, sensitive, accurate, precise, flexible and effective. This novel approach is able to deliver a superior level of performance in medical treatments over the existing modalities.
While microelectronic processes have been used for fabricating integrated circuit (“IC”) devices such as microprocessors, digital signal processors (“DSP”) and memory chips for the past two to three decades, their use has not been extended to most areas of bioscience and medicine. While there have been some application of micro-chips used in the area of laboratory diagnostic tests such as gene/DNA mapping and potential tests for diseases, their meaningful application in the areas of in-vivo diagnosis, drug delivery and disease treatments have not been utilized and are basically non-existent in the current state of the art.